GINSOMIN

Indications

• Management of photosensitivity reactions
• Erythropoietic protoporphyria

Dosage

Children: Child 1–4 years: 60–90 mg daily, Child 5–8 years: 90–120 mg daily, Child 9–11 years: 120–150 mg daily, to be given as a single dose or in divided doses.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Betacarotene acts as an antioxidant and a precursor to vitamin A, which plays a critical role in cellular function, vision, growth, immune function, and skin health.

Pharmacodynamics

As a provitamin, betacarotene is converted to retinol (vitamin A) in the body, supporting various biological functions, including the maintenance of epithelial tissues and the modulation of immune responses.

Pharmacokinetics

Betacarotene is absorbed from the gastrointestinal tract and is stored in the liver. Its absorption can be influenced by dietary fat intake. It is primarily metabolized in the liver and has a relatively long half-life due to its storage in fat tissues.

Pregnancy

Safety in pregnancy has not been established; use only if clearly needed.

Breast-feeding

Excretion in breast milk is unknown; use with caution.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Oral preparations containing beta-carotene

Indications

• Selenium deficiency
• Supportive therapy in conditions requiring antioxidant support
• Potential adjunct in cancer prevention strategies

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Initially 100–500 micrograms daily, adjusted according to response and serum levels.

Mechanism of action

Selenium is metabolized to selenophosphate and selenocysteine, which are essential for the synthesis of selenoproteins. This process involves the incorporation of selenium into proteins through a specialized tRNA that recognizes the RNA sequence UGA, which is facilitated by SECIS structures and SBP-2 proteins. Key selenoproteins, like glutathione peroxidases, help protect cells from oxidative damage, thus playing a significant role in reducing the risk of diseases such as atherosclerosis and certain cancers.

Pharmacodynamics

Selenium is incorporated into various selenoproteins that perform essential functions, including antioxidant activity, redox balance, and regulation of thyroid hormones. Its role in antioxidant defense mechanisms is particularly important for protecting cells against reactive oxygen species (ROS). Selenium supplementation has been linked to improved immune function and potential cancer prevention.

Pharmacokinetics

Selenium is absorbed through the gastrointestinal tract, and its bioavailability can vary based on the source and form of selenium. Once absorbed, it is distributed to various tissues, where it is incorporated into selenoproteins. Selenium is primarily excreted through urine, and its half-life can depend on dietary intake and individual metabolism. Selenium status can be assessed through blood levels of selenoproteins and selenium itself.

Adverse effects

• Nausea
• Anaemia
• Aplastic anaemia
• Skin reactions
• Gastrointestinal disorders

Precautions

• Selenium supplementation should not be given unless there is good evidence of deficiency.
• Use caution in patients with a history of hypersensitivity to selenium or its compounds.

Pregnancy

Limited information is available regarding selenium supplementation during pregnancy. Consult specialist sources for guidance.

Breast-feeding

Limited information is available; the effect of selenium on copper levels in milk is conflicting, and its impact on the infant is unknown.

Storage

After opening, store in a refrigerator (2–8°C).

Formulations

• Tablets (e.g., L-Selenomethionine 200 micrograms, SelenoPrecise 100 micrograms)
• Capsules (e.g., Trientine dihydrochloride 250 mg)
• Injection solutions (e.g., Sodium selenite 50 micrograms per 1 ml)

Indications

• Copper deficiency
• Occipital Horn Syndrome
• Menke's disease
• Contraception (via copper IUD)

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Refer to the relevant clinical guidelines and BNF for specific dosing information.

Mechanism of action

Copper is absorbed from the gastrointestinal tract via high affinity copper uptake proteins and low affinity copper uptake proteins, likely being reduced to the Cu1+ form prior to transport. Inside enterocytes, it binds to the copper transport protein ATOX1, which facilitates its transport to copper transporting ATPase-1 on the Golgi membrane for incorporation into the Golgi apparatus. Once in systemic circulation, copper binds primarily to ceruloplasmin, albumin, and alpha 2-macroglobulin. It acts as a cofactor in a variety of oxidase enzymes and also influences sperm motility when released from copper IUDs, contributing to its contraceptive effect.

Pharmacodynamics

Copper is essential for the activity of many enzymes and plays a vital role in processes such as iron metabolism, neurotransmitter synthesis, and antioxidant defense. Copper ions, particularly when released from intrauterine devices, have been shown to decrease sperm viability, thereby impacting fertility.

Pharmacokinetics

Copper is absorbed from the gut and is predominantly transported in the plasma bound to proteins such as ceruloplasmin and albumin. The absorption efficiency can vary; however, a significant portion of dietary copper is usually absorbed. The body regulates copper levels through hepatic excretion and storage mechanisms, ensuring homeostasis. Excess copper can lead to toxicity, while deficiency results in various health issues.

Pregnancy

Copper is considered essential during pregnancy, but excessive intake should be avoided due to potential toxicity.

Breast-feeding

Copper is excreted in breast milk, and adequate maternal intake is important for infant development.

Storage

Store in a cool, dry place, away from moisture and heat.

Mechanism of action

Folic acid is biochemically inactive until it is converted into active forms, primarily tetrahydrofolic acid and methyltetrahydrofolate, by the enzyme dihydrofolate reductase (DHFR). These active forms are essential for maintaining normal erythropoiesis, synthesizing nucleic acids, interconverting amino acids, and generating formate. They participate in critical one-carbon transfer reactions necessary for DNA synthesis and methylation processes. Folic acid, in conjunction with vitamin B12, helps normalize elevated homocysteine levels by facilitating its remethylation to methionine, a process that is crucial for various metabolic pathways.

Pharmacodynamics

Folic acid is an essential cofactor for enzymes involved in nucleic acid synthesis and amino acid metabolism. It is particularly significant in preventing megaloblastic anemia, which arises from impaired DNA synthesis due to folate deficiency. The synthesis of thymidylate, necessary for DNA formation, is directly influenced by folate availability. Folic acid's role is especially crucial during periods of rapid cellular division, and it has protective effects against certain cancer developments. As humans cannot synthesize folic acid endogenously, adequate dietary intake is essential for maintaining normal physiological functions.

Pharmacokinetics

Folic acid is absorbed in the small intestine and is then converted into its active forms within the body. The bioavailability of folic acid is influenced by factors such as food composition and the presence of certain gastrointestinal conditions. Once absorbed, it is transported in the bloodstream, mainly as 5-methyltetrahydrofolate. The distribution of folate occurs within various tissues, with significant

Adverse effects

• Allergic reactions
• Gastrointestinal disturbances
• Skin rash
• Altered sleep patterns

Interactions

• Anticonvulsants may reduce the effectiveness of folic acid
• Methotrexate may interfere with folic acid metabolism
• Trimethoprim-sulfamethoxazole can enhance the effects of folic acid deficiency

Precautions

• Monitor for signs of anemia in patients with malabsorption syndromes
• Use cautiously in patients with a history of hypersensitivity to folic acid
• Assess for vitamin B12 deficiency before initiating treatment, as folic acid can mask symptoms

Pregnancy

Folic acid is essential during pregnancy to prevent neural tube defects and support fetal development. Supplementation is recommended before conception and during the first trimester.

Breast-feeding

Folic acid passes into breast milk, and adequate maternal intake is important to ensure sufficient levels for the nursing infant.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral solutions
• Injectable forms

Indications

• Fatigue
• Stress management
• Cognitive enhancement
• Immune support
• General well-being

Dosage

Children: Refer to specific product guidelines, as dosing in children should be determined by a healthcare professional.

Adults: Refer to specific product guidelines, as dosing can vary based on formulation and intended use.

Mechanism of action

Ginseng is thought to exert its effects through several mechanisms, including modulation of the hypothalamic-pituitary-adrenal (HPA) axis, enhancement of antioxidant activity, and regulation of neurotransmitter levels. Ginsenosides, the active compounds in ginseng, may influence cellular signaling pathways, promote neuroprotection, and enhance immune responses.

Pharmacodynamics

The pharmacodynamic effects of ginseng are attributed primarily to its active constituents, ginsenosides, which interact with various receptors and enzymes in the body. These interactions can lead to increased energy metabolism, improved cognitive function, enhanced physical performance, and modulation of the immune system. Ginseng may also exhibit adaptogenic properties, helping the body to maintain homeostasis under stress.

Pharmacokinetics

Ginsenosides undergo extensive metabolism in the body, primarily by the liver. Bioavailability can vary significantly based on the specific ginsenoside and the method of administration. Ginseng is usually administered orally, with effects typically observed within several hours after ingestion. The elimination half-life of ginsenosides can vary based on the specific compound and individual metabolism, with some studies suggesting that effects may persist for several hours to days.

Adverse effects

• Insomnia
• Headache
• Gastrointestinal disturbances
• Nervousness
• Hypertension
• Allergic reactions

Interactions

• May interact with anticoagulants (e.g., warfarin)
• May enhance the effects of caffeine
• May affect insulin levels and blood sugar control
• Potential interaction with immunosuppressants

Precautions

• Use with caution in patients with hypertension
• May cause sleep disturbances; avoid use before bedtime
• Should be used cautiously in patients with diabetes
• Consult a healthcare provider before use in individuals with autoimmune conditions

Pregnancy

Limited data available. Generally not recommended due to potential hormonal effects.

Breast-feeding

Limited data available. Consult a healthcare provider before use.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Dried root
• Powdered extract
• Capsules
• Tinctures
• Teas

Indications

• Skin infections
• Fungal infections
• Wound care
• Dermatitis
• Eczema
• Disinfection of water

Dosage

Children: For paediatric use, potassium permanganate is also applied topically in diluted solutions. The concentration and duration should be determined by a healthcare professional based on the

Adults: For topical use, potassium permanganate is typically diluted in water to create a solution for washing or soaking affected areas, but specific concentrations and durations should be based on clinical guidelines or a healthcare professional's advice.

Mechanism of action

Potassium permanganate acts as an oxidizing agent. Upon contact with organic materials, it releases manganese ions which can disrupt the cellular processes of bacteria and other pathogens. This oxidative action leads to the denaturation of proteins and the disruption of cellular membranes, resulting in the antimicrobial effect. Additionally, it has astringent properties that can help to dry out and reduce inflammation in affected tissues.

Pharmacodynamics

The pharmacodynamics of potassium permanganate involve its activity as an antiseptic and astringent. Its oxidative properties allow it to effectively reduce microbial load on the skin and mucous membranes, making it useful in treating infections and inflammatory skin conditions. It also promotes wound healing by facilitating the removal of necrotic tissue and enhancing the granulation of healthy tissue.

Pharmacokinetics

Potassium permanganate is not significantly absorbed through the skin or mucous membranes when used topically. Its primary action is local, and it does not circulate in the bloodstream. The compound is excreted unchanged in the urine if absorbed systemically in significant amounts, which is rare. Its effects are primarily observed at the site of application, with the duration of action depending on the concentration and duration of exposure to the skin or mucous membranes.

Pregnancy

Manganese is categorized as FDA pregnancy category C. Animal reproduction studies have not been conducted, and it is not known whether manganese can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Breast-feeding

Manganese is excreted in human milk. Caution should be exercised when manganese is administered to a nursing woman.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Indications

• Pantothenate deficiency
• Support in energy metabolism
• Adjuvant therapy in chronic conditions requiring enhanced energy production

Dosage

Children: Refer to the BNF for Children for paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing information, generally 5-10 mg daily for adults.

Mechanism of action

Pantothenate functions primarily as a precursor to coenzyme A (CoA), which is vital for various biochemical reactions in the body. CoA is involved in the metabolism of fatty acids, the synthesis of cholesterol and steroid hormones, and the acetylation of various substrates, which is crucial for energy production and metabolic processes.

Pharmacodynamics

Pantothenate plays a significant role in energy metabolism, cellular respiration, and the biosynthesis of fatty acids. It facilitates the transfer of acyl groups, which is critical for the metabolism of carbohydrates and fats, thereby influencing the overall energy production in cells. Adequate levels of pantothenate are necessary for maintaining metabolic homeostasis and supporting growth and development.

Pharmacokinetics

Pantothenate is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 70%. Once absorbed, it is widely distributed throughout the body, particularly in the liver, adrenal glands, and kidneys. The vitamin is metabolized primarily in the liver, where it is converted to coenzyme A. Excess pantothenate is excreted in the urine as pantothenic acid and its metabolites. The half-life of pantothenate in the body is not well-defined but is generally considered to be relatively short due to its water-soluble nature.

Pregnancy

Pantothenic acid (Vitamin B5) is generally regarded as safe during pregnancy. It is important to maintain adequate levels for fetal development.

Breast-feeding

Pantothenic acid is excreted in breast milk in small amounts. Adequate intake is important for breastfeeding mothers, but supplementation is typically not necessary.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Pantothenate tablets
• Pantothenic acid capsules
• Pantothenate injections

Indications

• Vitamin deficiency syndromes (e.g., scurvy for vitamin C deficiency, rickets for vitamin D deficiency)
• Support for immune function
• Antioxidant support
• Bone health maintenance
• Vision health
• Energy metabolism support

Dosage

Children: Refer to the BNF for Children for specific vitamin dosing guidelines, which depend on age and nutritional requirements.

Adults: Refer to specific vitamin guidelines as dosage varies significantly depending on the type of vitamin and individual needs.

Mechanism of action

Vitamins function primarily as coenzymes or precursors for coenzymes in enzymatic reactions. For instance, B vitamins are involved in energy metabolism, while vitamins A, C, D, E, and K support various physiological functions including vision, antioxidant activity, calcium regulation, and blood clotting. Each vitamin has a unique mechanism of action based on its structure and role in the body.

Pharmacodynamics

Vitamins exert their effects at the cellular level, influencing metabolic pathways, gene expression, and immune responses. For example, vitamin D regulates calcium and phosphate homeostasis, while vitamin A is crucial for vision and immune function. Deficiencies in vitamins can lead to a range of disorders, highlighting their importance in maintaining health.

Pharmacokinetics

The pharmacokinetics of vitamins vary widely. Fat-soluble vitamins (A, D, E, and K) are stored in liver and adipose tissues and can be released into circulation as needed. Water-soluble vitamins (B-complex and C) are not stored and must be consumed regularly, with excess amounts excreted in urine. Absorption rates, half-lives, and distribution can also differ based on the specific vitamin and individual metabolic factors.

Interactions

• tretinoin+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Moderate (increases risk of toxicity)
• carbamazepine+vitamin: Unknown (decreases effects)
• cobicistat+vitamin: Unknown (increases exposure)
• vitamin D substances+digoxin: Unknown (increases risk of toxicity)
• idelalisib+vitamin: Unknown (increases exposure)
• clarithromycin+vitamin: Unknown (increases exposure)

Pregnancy

Consult healthcare professional before use. Vitamin supplementation during pregnancy should be carefully managed to avoid hypervitaminosis.

Breast-feeding

Consult healthcare professional before use. Some vitamins can pass into breast milk and may affect the infant.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure it is kept out of reach of children.

Formulations

• {'name': 'Vitamin A', 'form': 'Capsule', 'strength': '10000 IU'}
• {'name': 'Vitamin D', 'form': 'Tablet', 'strength': '1000 IU'}
• {'name': 'Vitamin E', 'form': 'Softgel', 'strength': '400 IU'}

Indications

• Zinc deficiency
• Magnesium deficiency
• Support for immune function
• Muscle cramping
• Exercise recovery
• General health and well-being

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional.

Adults: Refer to specific product guidelines or consult a healthcare professional.

Mechanism of action

Zinc acts as a cofactor for numerous enzymes and is involved in the regulation of gene expression. It also influences the immune system by affecting the formation and activity of immune cells. Magnesium plays a role in neuromuscular transmission and can help regulate calcium levels in cells, promoting muscle relaxation and preventing spasms. Together, these minerals may enhance muscle function and recovery, as well as support immune responses.

Pharmacodynamics

The pharmacodynamic effects of zinc and magnesium include modulation of enzyme activities, regulation of neurotransmitter release, and participation in energy metabolism. Zinc is known to enhance the activity of over 300 enzymes that facilitate biochemical reactions, while magnesium is involved in ATP production and stabilization of cellular structures. The synergistic effect of these minerals may contribute to improved muscle performance and reduced fatigue.

Pharmacokinetics

Zinc is primarily absorbed in the small intestine, with absorption efficiency influenced by dietary factors and the presence of other minerals. It is distributed throughout the body, with significant concentrations in the liver, muscle, and bone. Zinc is excreted mainly through the feces, with some loss occurring through urine. Magnesium absorption occurs in the small intestine as well, with bioavailability affected by dietary composition and individual physiological factors. Magnesium is distributed in bone, muscle, and soft tissues, and it is excreted primarily via the kidneys.

Adverse effects

• Nausea
• Diarrhea
• Stomach upset
• Metallic taste
• Allergic reactions

Interactions

• May interact with certain antibiotics (e.g., tetracyclines, quinolones) reducing their absorption
• May affect the absorption of other minerals such as copper and iron

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of zinc toxicity in high doses
• Assess dietary intake before supplementation

Pregnancy

Zinc is essential for fetal development, but high doses should be avoided. Consult a healthcare provider for supplementation.

Breast-feeding

Zinc is excreted in breast milk and is important for infant development. Consult a healthcare provider for appropriate dosing.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Zinc-magnesium supplements in tablet or capsule form
• Liquid formulations available

Mechanism of action

Beta-carotene is an antioxidant that presents significant efficacy against the reactive oxygen species singlet oxygen. Beta-carotene acts as a scavenger of lipophilic radicals within the membranes of every cell compartments. It also presents an oxidative modification of LDL. The presence of long chains of conjugated double bonds is responsible for its antioxidative properties by allowing beta-carotene to chelate oxygen-free radicals and dissipate their energy. The chelation of free radicals inhibits the peroxidation of lipids. The effect of beta-carotene in the immune response is thought to be related to the direct effect on the thymus which increases the production of immune cells. IN HEMATOPORPHYRIN PHOTOSENSITIZED MICE BETA-CAROTENE SHOWED PHOTOPROTECTION WAS DUE TO FREE RADICAL SCAVENGING OR SINGLET O QUENCHING BUT ALSO A POSSIBLE ROLE OF 400 NM LIGHT ABSORPTION, A PROPERTY OF BETA-CAROTENE. Beta carotene protects patients with erythropoietic protoporphyria against severe photosensitivity reactions (burning sensation, edema, erythema, pruritus, and/or cutaneous lesions). The drug has no effect on the basic biochemical abnormality of erythropoietic protoporphyria (eg, erythrocyte, plasma, and stool concentrations of protoporphyrins are not altered by the drug). The precise mechanism by which the drug exerts photoprotection has not been established. There is some evidence that photosensitizers may act through the formation of singlet excited oxygen and/or free radicals. Since in vitro studies indicate that beta carotene can quench free radicals and singlet excited oxygen, this may be the mechanism by which the drug acts. It is unlikely that beta carotene acts simply as a filter for the wavelengths of light that induce phototoxic effects. beta-Carotene inhibits UV-B carcinogenesis. beta-Carotene is an excellent quencher of singlet oxygen, and can quench free radicals. beta-Carotene has been shown to quench singlet oxygen/free radical reactions in the skin of porphyric mice, and has been found to quench excited species formed on irradiation of mouse skin by UV-B.

Pharmacodynamics

Oral administration of beta-carotene increases the serum concentration of beta-carotene by 60% but it does not change the concentration found in the heart, liver or kidneys. In vitro studies in hepatocytes have shown that beta-carotene ameliorates oxidative stress, enhances antioxidant activity and decreases apoptosis. Other than the antioxidant activities, some other actions have been correlated to beta-carotene. It is thought to have detoxifying properties, as well as to help increase resistance to inflammation and infection and increase immune response and enhance RNA production.

Mechanism of action

Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA. This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Selenoproteins appear to be necessary for life as mice with the specialized tRNA gene knocked out exhibited early embryonic lethality. The most important selenoproteins seem to be the glutathione peroxidases and thioredoxin reductases which are part of the body's defenses againts reactive oxygen species (ROS). The importance of selenium in these anti-oxidant proteins has been implicated in the reduction of atherosclerosis by preventing the oxidation of low density lipoprotein. Selenium supplementation is also being investigated in the prevention of cancer and has been suggested to be beneficial to immune function. Converging data from epidemiological, ecological, and clinical studies have shown that selenium (Se) can decrease the risk for some types of human cancers. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. Prior to occurrence of apoptosis, Se compounds alter the expression and/or activities of signaling molecules, mitochondria-associated factors, transcriptional factors, tumor suppressor genes, and cellular reduced glutathione. Mechanistic studies have demonstrated that the methylselenol metabolite pool has many desirable attributes of chemoprevention, whereas the hydrogen selenide pool with excess of selenoprotein synthesis can lead to DNA single-strand breaks. To elucidate the effects of Se on cytotoxic events, it should be remembered that the chemical forms and the dose of Se, and the experimental system used, are determinants of its biological activities. This mini-review focuses on elucidation of the molecular mechanisms of cancer prevention by Se with the apoptotic approach. /Selenium/ Selenium status can also influence thyroid hormone function via the deiodinase enzymes. Selenium is a critical component of the deiodinase enzymes, including iodothyronine 5'-deiodinases, which convert the prohormone thyroxine (T4) to the active circulating form, triiodothyronine (T3). Selenium is also a component of GPX, the main enzyme responsible for protecting thyroid cells against oxidative damage. GPX is involved in the detoxification of hydrogen peroxide, which is produced in the thyroid during the conversion of T4 to T3. /Selenium/ Selenium readily substitutes for sulfur in biomolecules and in many biochemical reactions, especially when the concentration of selenium is high and the concentration of sulfur is low in the organism. Inactivation of the sulfhydryl enzymes necessary for oxidative reactions in cellular respiration, through effects on mitochondrial and microsomal electron transport, might contribute to acute selenium toxicity. Selenium may have a role in hepatic heme metabolism that is related to GPX or lipid peroxidation. Selenocysteine is specifically found in some proteins (e.g., glutathione peroxidase); selenomethionine appears to randomly substitute for methionine in protein synthesis. This appears to be an additional mechanism for intermediate- or chronic-duration toxicity. Skin, hair, and nail damage are significant indicators of chronic selenium overexposure. The mechanism causing these integumentary effects is unclear, but could be related to the high selenium concentrations in these tissues as a consequence of the substitution of selenium for sulfur in certain amino acids, including the disulfide bridges that pr

Pharmacodynamics

Selenium is incorporated into many different selenoproteins which serve various functions throughout the body.

Mechanism of action

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2. It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%). Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor. It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor. Copper appears to reduce the viabilty and motility of spermatozoa. This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect. The exact mechanism of copper's effect on sperm are unknown. The reason for the less severe reaction when the foreign body is at a distance from the retina has been proposed to be ... that near the retina & its blood vessels there is greater oxygen tension than at a distance, which causes metallic copper to oxidize to toxic copper compounds more rapidly close to or in contact with the retina than at a distance. Furthermore, the abscess formation that is characteristic of copper undergoing oxidation close to the retina & choroiod can be attributed to attraction of polymorphonuclear leukocytes from these nearby vascular tissues, which become heavily infiltrated. Liquefaction & disorganization of the vitreous body has been explained on the basis of copper catalysis of oxidation of ascorbic acid, leading to depolymerization of the hyaluronic acid of the vitreous humor. Changes in protein & hexosamine content have also been related to decrease in viscosity of the vitreous humor. Increased content of amino acids in the vitreous humor has been consistent with proteolysis of the vitreous body, but decreased concentration in the aqueous humor has suggested suppression of secretion of amino acids by the ciliary body under the influence of copper.

Pharmacodynamics

Copper is incorporated into many enzymes throughout the body as an essential part of their function. Copper ions are known to reduce fertility when released from copper-containing IUDs.

Mechanism of action

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase. Folic acid, after conversion to tetrahydrofolic acid, is necessary for normal erythropoiesis, synthesis of purine and thymidylates, metabolism of amino acids such as glycine and methionine, and the metabolism of histidine. The principal biochemical function of folates is the mediation of one-carbon transfer reactions. 5-Methyltetrahydrofolate donates a methyl group to homocystine, in the conversion of homocystine to L-methionine. ... 5,10-Methyltetrahydrofolate is regenerated from tetrahydrofolate via the enzyme serine hydroxymethyltransferase, a reaction, which in addition to producing 5,10-methyltetrahydrofolate, yields glycine. ... 5,10-methyltetrahydrofolate, supplies the one carbon group for the methylation of deoxyuridylic acid to form the DNA precursor thymidylic acid. This reaction is catalyzed by thymidylate synthase and the folate product of the reaction is dihydrofolate. Dihydrofolate is converted to tetrahydrofolate via the enzyme dihydrofolate reductase ...

Pharmacodynamics

Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as [DB00563] as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.